Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2015; 21(14): 4216-4224
Published online Apr 14, 2015. doi: 10.3748/wjg.v21.i14.4216
Th22 cell accumulation is associated with colorectal cancer development
Yong-Hong Huang, Yun-Fei Cao, Zhi-Yuan Jiang, Sen Zhang, Feng Gao
Yong-Hong Huang, Yun-Fei Cao, Zhi-Yuan Jiang, Sen Zhang, Feng Gao, Department of Colorectal and Anal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Author contributions: Huang YH and Cao YF contributed equally to this work; Gao F designed the research; Zhang S and Cao YF contributed new reagents; Jiang ZY and Huang YH performed research; Cao YF and Huang YH analyzed data; and Huang YH wrote the paper.
Supported by National Natural Science Foundation of China, No. 81260316 and No. 81260335.
Ethics approval: This study was reviewed and approved by the First Affiliated Hospital of Guangxi Medical University Institutional Review Board.
Institutional animal care and use committee: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the First Affiliated Hospital of Guangxi Medical University (IACUC No: 201402068).
Conflict-of-interest: The authors report no conflicts of interest in this work.
Data sharing: The technical appendix, statistical code, and dataset are available from the corresponding author at doctorgao0771@hotmail.com. All participants gave informed consent for data sharing.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Feng Gao, Professor, Department of Colorectal and Anal Surgery, First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China. doctorgao0771@hotmail.com
Telephone: +86-771-5356529 Fax: +86-771-5351442
Received: October 26, 2014
Peer-review started: October 27, 2014
First decision: November 14, 2014
Revised: November 27, 2014
Accepted: January 16, 2015
Article in press: January 16, 2015
Published online: April 14, 2015
Processing time: 170 Days and 22 Hours
Abstract

AIM: To investigate the expression of Th22 cells and related cytokines in colorectal cancer (CRC) tissues, and the probably mechanism.

METHODS: CRC tumor and paratumor tissues were collected to detect the expression levels of Th22 cells and of related cytokines by immunohistochemistry, flow cytometry and real-time quantitative polymerase chain reaction (RT-qPCR). Interleukin (IL)-22 alone or with a STAT3 inhibitor was co-cultured with RKO cells in vitro to study the effects of IL-22 on colon cancer cells. IL-22 alone or with a STAT3 inhibitor was injected into a BALB/c nude mouse model with subcutaneously transplanted RKO cells to study the effects of IL-22 on colon cancer growth.

RESULTS: The percentage of Th22 cells in the CD4+ T subset was significantly higher in tumor tissues compared with that in paratumor tissues (1.47% ± 0.083% vs 1.23% ± 0.077%, P < 0.05) as determined by flow cytometry. RT-qPCR analysis revealed that the mRNA expression levels of IL-22, aryl hydrocarbon receptor, CCL20 and CCL22 were significantly higher in tumor tissues compared with those in paratumor tissues. CCL27 mRNA also displayed a higher expression level in tumor tissues compared with that in paratumor tissues; however, these levels were not significantly different (2.58 ± 0.93 vs 2.30 ± 0.78, P > 0.05). IL-22 enhanced colon cancer cell proliferation in vitro and displayed anti-apoptotic effects; these effects were blocked by adding a STAT3 inhibitor. IL-22 promoted tumor growth in BALB/c nude mice; however, this effect was reversed by adding a STAT3 inhibitor.

CONCLUSION: Th22 cells that accumulate in CRC may be associated with the chemotactic effect of the tumor microenvironment. IL-22 is associated with CRC development, most likely via STAT3 activation.

Keywords: Th22 cells; Interleukin-22; STAT3; Colorectal cancer; Tumor microenvironment

Core tip: Although the functional characteristics of Th22 cells in inflammatory and autoimmune diseases have been extensively studied, their role in colorectal cancer (CRC) remains unclear. This study demonstrated the differences in the expression of Th22 cells and their related cytokines between colorectal tumor and paratumor tissues and the accumulation of Th22 cells in CRC may be associated with the functions of chemotactic factors that are secreted by the tumor microenvironment. Interleukin-22 was found to be the functional factor of Th22 cells that is associated with CRC development in both in vitro and in vivo experiments, most likely via STAT3 pathway activation.